Alternative names
MXE
IUPAC Name
(RS)2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone
Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Chemically, methoxetamine (MXE) is 2-(ethylamino)-2-(3-methoxyphenyl) cyclohexanone. It is a synthetic drug and belongs to the arylcyclohexylamine class, like phencyclidine. Methoxetamine has two enantiomers and is commonly available as the racemic mixture.
Previous review
During its thirty-sixth meeting, the WHO ECDD discussed the critical review report on methoxetamine and concluded that owing to the insufficiency of data regarding dependence, abuse and risks to public health, methoxetamine should not be placed under international control at that time, but be kept under surveillance. In 2014, the European Union decided to bring methoxetamine under control after a risk assessment by the EMCDDA. Furthermore, new information on its abuse potential and more reports of fatal and non-fatal intoxications warranted a critical review at the thirty-seventh meeting of the ECDD.
Similarity to known substances and effects on the central nervous system
Methoxetamine binds to the N-methyl-D-aspartate (NMDA) glutamate receptor similar to ketamine and phencyclidine, but unlike ketamine it also binds to the SERT. It is possible that inhibition of SERT may contribute to both its psychopharmacological profile and its increased risk of toxicity compared to ketamine.
While methoxetamine is classified within the same pharmacological class as PCP and ketamine, its reported effects appear to differ from those of ketamine, suggesting that its actions in the brain may overlap with, but are not the same as, those of ketamine. In addition, the methoxetamine doses that produce the expected and toxic effects overlap, making this compound particularly dangerous.
Dependence potential
No dependence studies have been conducted with methoxetamine. Information from user websites is suggestive. One user reported craving, an escalation in dosage, and feelings of being "detached and sad" during abstinence, but apparently had no withdrawal signs indicative of physical dependence.
Actual abuse and/or evidence of likelihood of abuse
In nonclinical studies, methoxetamine produces conditioned place preference in rats comparable to the effect of ketamine, and is self-administered, but not robustly, suggesting some potential for abuse. Clinical abuse liability studies have not been conducted. Information from other official sources is not available. Some inferences can be made from information on user websites. Desired psychological and behavioural effects reported on such websites include: euphoria, empathy, pleasant intensification of sensory experiences, mild to strong sense of dissociation from the physical body, de-realization, improved social interaction, distorted sense of reality and vivid hallucinations. A total of 120 non-fatal intoxications and 22 deaths associated with methoxetamine have been reported. Methoxetamine use has been reported from an increasing number of countries including: Austria, Belgium, Canada, Estonia, Finland, France, Italy, the Netherlands, Norway, Poland, Russian Federation, Singapore, Spain, Sweden, Ukraine, The United Kingdom of Great Britain and Northern Ireland and the United States.
Therapeutic usefulness
There is no evidence that methoxetamine is used therapeutically.
Recommendation
Methoxetamine has been shown to have effects similar to phencyclidine, a compound listed in Schedule II of the Convention on Psychotropic Substances of 1971. The Committee considered that the degree of risk to public health and society associated with the abuse liability of methoxetamine is substantial. The Committee also noted it has no recorded therapeutic use. The Committee considered that the evidence of its abuse warranted its placement under international control. The Committee therefore recommended that methoxetamine be placed in Schedule II of the 1971 Convention.
Chemically, methoxetamine (MXE) is 2-(ethylamino)-2-(3-methoxyphenyl) cyclohexanone. It is a synthetic drug and belongs to the arylcyclohexylamine class, like phencyclidine. Methoxetamine has two enantiomers and is commonly available as the racemic mixture.
Previous review
During its thirty-sixth meeting, the WHO ECDD discussed the critical review report on methoxetamine and concluded that owing to the insufficiency of data regarding dependence, abuse and risks to public health, methoxetamine should not be placed under international control at that time, but be kept under surveillance. In 2014, the European Union decided to bring methoxetamine under control after a risk assessment by the EMCDDA. Furthermore, new information on its abuse potential and more reports of fatal and non-fatal intoxications warranted a critical review at the thirty-seventh meeting of the ECDD.
Similarity to known substances and effects on the central nervous system
Methoxetamine binds to the N-methyl-D-aspartate (NMDA) glutamate receptor similar to ketamine and phencyclidine, but unlike ketamine it also binds to the SERT. It is possible that inhibition of SERT may contribute to both its psychopharmacological profile and its increased risk of toxicity compared to ketamine.
While methoxetamine is classified within the same pharmacological class as PCP and ketamine, its reported effects appear to differ from those of ketamine, suggesting that its actions in the brain may overlap with, but are not the same as, those of ketamine. In addition, the methoxetamine doses that produce the expected and toxic effects overlap, making this compound particularly dangerous.
Dependence potential
No dependence studies have been conducted with methoxetamine. Information from user websites is suggestive. One user reported craving, an escalation in dosage, and feelings of being "detached and sad" during abstinence, but apparently had no withdrawal signs indicative of physical dependence.
Actual abuse and/or evidence of likelihood of abuse
In nonclinical studies, methoxetamine produces conditioned place preference in rats comparable to the effect of ketamine, and is self-administered, but not robustly, suggesting some potential for abuse. Clinical abuse liability studies have not been conducted. Information from other official sources is not available. Some inferences can be made from information on user websites. Desired psychological and behavioural effects reported on such websites include: euphoria, empathy, pleasant intensification of sensory experiences, mild to strong sense of dissociation from the physical body, de-realization, improved social interaction, distorted sense of reality and vivid hallucinations. A total of 120 non-fatal intoxications and 22 deaths associated with methoxetamine have been reported. Methoxetamine use has been reported from an increasing number of countries including: Austria, Belgium, Canada, Estonia, Finland, France, Italy, the Netherlands, Norway, Poland, Russian Federation, Singapore, Spain, Sweden, Ukraine, The United Kingdom of Great Britain and Northern Ireland and the United States.
Therapeutic usefulness
There is no evidence that methoxetamine is used therapeutically.
Recommendation
Methoxetamine has been shown to have effects similar to phencyclidine, a compound listed in Schedule II of the Convention on Psychotropic Substances of 1971. The Committee considered that the degree of risk to public health and society associated with the abuse liability of methoxetamine is substantial. The Committee also noted it has no recorded therapeutic use. The Committee considered that the evidence of its abuse warranted its placement under international control. The Committee therefore recommended that methoxetamine be placed in Schedule II of the 1971 Convention.
ECDD Recommendation
Inclusion in Schedule II of the 1971 Convention on Psychotropic Substances
Link to full TRS
who_trs_998_eng.pdf330.66 KB
MS Questionnaire Report